Digitalis drugs have long been used for treatment of congestive heart failure and atrial arrhythmia. They are well tolerated and patient compliance is good. We have confirmed and extended earlier observations that acetyl strophanthidin (AS), an ultra rapidly acting digitalis drug, suppresses ventricular premature beats (VPBs) in up to 50% of patients. Our results indicate that this response is not limited to AS. In fact, the reduction of VPBs observed with AS can be replicated with digoxin. We have now demonstrated that the positive inotropic effect of the cardiac glycosides does not appear to be the key factor accounting for the reduction in VPB frequency and grade. Our preliminary data indicates that digitalis-induced enhancement in vagus nerve activity may be the mechanism accounting for the antiarrhythmic action. We have demonstrated that quinidine reduces digoxin clearance as well as contracts the space of its distribution. Goals for the coming year include: (1) Determining the type of patients who respond to glycoside-induced VPB suppression; (2) Providing additional data on the role of the vagus and probing precise mechanisms; (3) Studying interaction of various antiarrhythmic drugs with digitalis glycosides.